Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment-related mortality due to infectious complications following potentially curable aggressive chemotherapy remains a major clinical problem. However, the diagnosis of neutropenic infections is difficult. Although it is common practice to institute empirical broad-spectrum antibiotics in neutropenic fever, liberal use of antibiotics may contribute to increasing resistance and superinfection such as systemic mycosis. Clinicians are searching for a highly specific and sensitive marker indicating early infection. Serum concentrations of several acute-phase proteins (C-reactive protein, serum amyloid A), proinflammatory cytokines (TNFalpha, IL-1, IFNgamma, IL-6, IL-8), soluble adhesion molecules (soluble E-selectin, vascular cell adhesion molecule 1, intercellular adhesion molecule 1) and more recently procalcitonin have been investigated as to whether these may contribute to identifying infections as the cause of neutropenic fever. Unfortunately, at present, based on the small and inconsistent amount of data available from the literature one is tempted to conclude that the predictive values of all these parameters are too low to influence the clinically based initial treatment decisions in patients with neutropenic fever.
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PMID:Evaluation of neutropenic fever: value of serum and plasma parameters in clinical practice. 1067 56

High density lipoprotein (HDL) and its main apolipoproteins, AI and serum amyloid A (SAA), present in physiological and acute phase response conditions, respectively, affect the inflammatory process. This study focuses on the effect of AI, SAA, and HDL from healthy (N-HDL) and acute phase individuals (AP-HDL) on the release of TNF-alpha, IL-1beta, and IL-8 by human blood neutrophils. It was observed that SAA (100 microg/mL) causes a dramatic increase (75-400 times) in the basal liberation of the three cytokines assayed. This effect is not triggered by AP-HDL. Although AI (100 microg/ml) increases the release of IL-1beta and IL-8 modestly, N-HDL does not. Both HDLs (0.16-0.32 mg of protein/mL) had an anti-inflammatory action, decreasing the basal and LPS-stimulated cytokine release. Given that the biological role of SAA is still uncertain, the present study adds an important finding potentially pertinent to the biological role of this acute phase protein.
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PMID:A novel function of serum amyloid A: a potent stimulus for the release of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-8 by human blood neutrophil. 1067 17

To study local lung inflammation, 34 subjects had endotoxin (1-4 ng/kg) instilled into a lung segment and saline instilled into a contralateral segment followed by bronchoalveolar lavage (BAL) at 2 h, 6 h, 24 h, or 48 h. Endotoxin instillation resulted in a focal inflammatory response with a distinct time course. An early phase (2 h to 6 h) revealed an increase in neutrophils (p = 0.0001) with elevated cytokines (tumor necrosis factor [TNF]-alpha, TNF receptors [TNFR], interleukin [IL]-1beta, IL-1 receptor antagonist, IL-6, granulocyte-colony-stimulating factor [G-CSF], all p < or = 0.002, but no change in IL-10) and chemokines (IL-8, epithelial neutrophil activating protein-78, monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, all p < or = 0.001, but no change in growth-regulated peptide-alpha). A later phase (24 h to 48 h) showed increased neutrophils, macrophages, monocytes, and lymphocytes (all p < or = 0.02), and a return to basal levels of most mediators. Elevated levels of inflammatory markers (TNFR(1), TNFR(2), L-selectin, lactoferrin, and myeloperoxidase) persisted in the BAL at 48 h (p < or = 0.001). Increased permeability to albumin occurred throughout both phases (p = 0.001). Blood C-reactive protein, serum amyloid A, IL-6, IL-1ra, G-CSF, but not TNF-alpha increased by 8 h (all p < or = 0.008). The local pulmonary inflammatory response to endotoxin has a unique qualitative and temporal profile of inflammation compared with previous reports of intravenous endotoxin challenges. This model provides a means to investigate factors that initiate, amplify, and resolve local lung inflammation.
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PMID:Local inflammatory responses following bronchial endotoxin instillation in humans. 1140 64

Host response to injury and infection is accompanied by a rapid rise in the blood of acute-phase proteins such as serum amyloid A (SAA). Although SAA has been used as a marker for inflammatory diseases, its role in the modulation of inflammation and immunity has not been defined. Human neutrophils respond to SAA with secretion of the proinflammatory cytokines interleukin 8 (IL-8) and, to a lesser extent, tumor necrosis factor alpha (TNF-alpha). The induction of IL-8 secretion by SAA involves both transcription and translation and correlates with activation of nuclear factor kappaB (NF-kappaB). The proximal signaling events induced by SAA include mobilization of intracellular Ca(2+) and activation of the mitogen-activated protein kinases ERK1/2 and p38, both required for the induced IL-8 secretion. Pertussis toxin effectively blocks SAA-induced IL-8 secretion indicating involvement of a Gi-coupled receptor. Overexpression of FPRL1/LXA4R in HeLa cells results in a significant increase of the expression of NF-kappaB and IL-8 luciferase reporters by SAA, and an antibody against the N-terminal domain of FPRL1/LXA4R inhibits IL-8 secretion. Lipoxin A4, which binds to FPRL1/LXA4R specifically, decreases SAA-induced IL-8 secretion significantly. Collectively, these results indicate that the cytokine-like property of SAA is manifested through activation of the Gi-coupled FPRL1/LXA4R, which has been known to mediate the anti-inflammatory effects of lipoxin A4. The ability of FPRL1/LXA4R to mediate 2 drastically different and opposite functions suggests that it plays a role in the modulation of inflammatory and immune responses.
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PMID:Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R. 1239 91

This work reports the effect of the apolipoproteins A-I and A-II (apoA-I and apoA-II) on the release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist (IL-1Ra) and on the oxidative burst of human neutrophils. By themselves, apoA-I and apoA-II do not affect the basal liberation of these cytokines, whereas apoA-I affects the release of IL-1beta from lipopolysaccharide (LPS)-stimulated neutrophils and apoA-II affects IL-8 released from LPS-stimulated neutrophils. ApoA-II also decreases the production of IL-8 released by neutrophils stimulated with the acute phase apolipoprotein serum amyloid A. Both apoA-I and apoA-II exerted approximately 30% inhibition on the oxidative burst of neutrophils stimulated by opsonized zymosan, as revealed by the luminol-enhanced chemiluminescence assay. These findings give additional support to the idea that the role of human plasma lipoproteins and apolipoproteins goes beyond their function in lipid transport and metabolism. HDL apolipoproteins appear to be a class of mediators that can participate in the regulation of the activity of neutrophils.
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PMID:Apolipoproteins A-I and A-II downregulate neutrophil functions. 1245 30

The acute phase response is a systemic reaction to inflammatory processes characterized by multiple physiological adaptations, including the hepatic synthesis of acute-phase proteins. In humans, serum amyloid A (SAA) is one of the most prominent of these proteins. Despite the huge increase of serum levels of SAA in inflammation, its biological role remains to be elucidated, even though SAA is undoubtedly active in neutrophils. In a previous study, we reported that SAA induces the release of tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-8 from human blood neutrophils. Here, we extend our earlier study, focusing on the effect of SAA on neutrophil IL-8 transcription and on the signaling pathways involved. We demonstrate herein that SAA, in relatively low concentrations (0.4-100 microg/ml) compared with those found in plasma in inflammatory conditions, induces a dose-dependent release of IL-8 from neutrophils. The p38 mitogen-activated protein kinase inhibitor SB 203580 inhibits the IL-8 mRNA expression and the release of protein from neutrophils. The release of IL-8 from SAA-stimulated neutrophils is strongly suppressed by the addition of N-acetyl-l-cysteine, alpha-mercaptoethanol, glutathione, and dexamethasone. SAA also induces IL-8 expression and release from monocytes. In conclusion, SAA appears to be an important mediator of the inflammatory process, possibly contributing to the pool of IL-8 produced in chronic diseases, which may play a role in degenerative diseases.
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PMID:mRNA expression and release of interleukin-8 induced by serum amyloid A in neutrophils and monocytes. 1285 1

Recently, we described the effect of the acute phase protein serum amyloid A (SAA) on the mRNA expression and release of IL-8 in neutrophils [Mediators Inflamm. 12 (3) (2003) 173]. Here, we expand this earlier study, focusing on tumor necrosis factor-alpha (TNF-alpha) m-RNA expression and protein release. Our findings indicate that SAA stimulates the rapid expression and release of TNF-alpha from cultured human blood neutrophils. The release of TNF-alpha from SAA-stimulated neutrophils is strongly suppressed by the addition of the antioxidants N-acetyl-L-cysteine, alpha-mercaptoethanol, glutathione, the antiinflammatory dexamethasone and the compounds wortmannin (a PI3K inhibitor), PD98059 (a MEK-1 inhibitor) and SB203580 (a p38 inhibitor). Monocytes also responded to SAA by releasing TNF-alpha. These data are congruent with the increasing evidence of the role of SAA in modulating inflammatory and immune responses, possibly contributing to the pool of cytokines produced in acute inflammation and in chronic diseases.
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PMID:Serum amyloid A-induced mRNA expression and release of tumor necrosis factor-alpha (TNF-alpha) in human neutrophils. 1475 67

Mammary gland epithelial cells are likely to be important effectors in defending against mastitis, yet little is known about their response mechanisms. Here, we describe a cryopreserved bovine mammary epithelial cell model to study the infection response. Primary cell cultures from four Holstein cows were prepared, and frozen after two passages. The cell cultures from each cow were then thawed and maintained separately, yet simultaneously, and exposed to treatments that included infection with Staphylococcus aureus or exposure to LPS from Escherichia coli. A clear inflammatory response was shown by a significant (P < 0.05), dose dependent, increase of lactoferrin and IL-8 secretion within 24h in response to S. aureus or LPS. Marked increases (P < 0.05) in lactoferrin, TNF-alpha and serum amyloid A (SAA) mRNA expression were also observed. The results indicate the usefulness of our model to study infection responses of mammary epithelial cells, where all cells are simultaneously exposed to the same infection pressure. These responses can be studied over time, and most importantly, biological replication is provided by the four different genotypes being investigated individually. Finally, the results indicate that mammary epithelial cells play an important role in inflammatory response, through the production of pro-inflammatory cytokines, an acute phase protein, and lactoferrin.
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PMID:Cryopreserved bovine mammary cells to model epithelial response to infection. 1535 Jul 49

White adipose tissue is now recognised to be a multifunctional organ; in addition to the central role of lipid storage, it has a major endocrine function secreting several hormones, notably leptin and adiponectin, and a diverse range of other protein factors. These various protein signals have been given the collective name 'adipocytokines' or 'adipokines'. However, since most are neither 'cytokines' nor 'cytokine-like', it is recommended that the term 'adipokine' be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes. It is suggested that the term is restricted to proteins secreted from adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue. The adipokinome (which together with lipid moieties released, such as fatty acids and prostaglandins, constitute the secretome of fat cells) includes proteins involved in lipid metabolism, insulin sensitivity, the alternative complement system, vascular haemostasis, blood pressure regulation and angiogenesis, as well as the regulation of energy balance. In addition, there is a growing list of adipokines involved in inflammation (TNFalpha, IL-1beta, IL-6, IL-8, IL-10, transforming growth factor-beta, nerve growth factor) and the acute-phase response (plasminogen activator inhibitor-1, haptoglobin, serum amyloid A). Production of these proteins by adipose tissue is increased in obesity, and raised circulating levels of several acute-phase proteins and inflammatory cytokines has led to the view that the obese are characterised by a state of chronic low-grade inflammation, and that this links causally to insulin resistance and the metabolic syndrome. It is, however, unclear as to the extent to which adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and whether there is a generalised or local state of inflammation. The parsimonious view is that the increased production of inflammatory cytokines and acute-phase proteins by adipose tissue in obesity relates primarily to localised events within the expanding fat depots. It is suggested that these events reflect hypoxia in parts of the growing adipose tissue mass in advance of angiogenesis, and involve the key controller of the cellular response to hypoxia, the transcription factor hypoxia inducible factor-1.
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PMID:Adipokines: inflammation and the pleiotropic role of white adipose tissue. 1546 38

Familial Mediterranean Fever (FMF), also known as paroxysmal polyserositis, is an autosomal recessive disease affecting mainly Mediterranean populations (Jews, Armenians, Arabs, Turks). It is characterised by recurrent crises of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. Erysipela-like erythema affecting mainly feet and legs and effort-induced myalgia are less frequently encountered symptoms. The major complication of FMF is the development of renal amyloidosis. Standard laboratory tests of FMF patients are non-informative, except for the high sedimentation rate and white blood cell count, but during and immediately after crises, diminished albumin concentrations and elevated fibrinogen, C-reactive protein, beta2 and alpha2 M globulins, haptoglobin and lipoprotein concentrations are noted. Studies have measured immunoglobulin (Ig) levels in the sera of FMF patients and found elevated levels of IgA, IgM, IgG, and IgD in 23%, 13%, 17% and 13%, respectively. FMF crises are characterised by a massive influx of polymorphonuclear leukocytes into the inflamed regions. Moreover, the peritoneal fluid of FMF patients contains abnormally low levels of the inhibitor of complement fragment C5a and interleukin 8. Failure to suppress inflammatory response to C5a may explain the typical inflammatory FMF crises. The MEFV (for MEditerranean FeVer) gene responsible for the disease has been identified on 16p13.3. It is composed of 10 exons and spans approximately 14 Kb of genomic DNA. More than 35 mutations have so far been identified. The most frequent are M694V, M694I, M680I, V726A and E148Q. The M694V mutation is the most frequent mutation in the various ethnic groups considered, although its frequency varies from group to group. The V726A mutation is observed mainly among Ashkenazi and Iraqi Jews, Druzes and Armenians, and the M680I among Armenians and Turks. M694I and A744S seem specific to Arab populations, and R761H is frequently found in Lebanese FMF patients. The M694V mutation is often correlated with severe phenotypes, mainly in the homozygous state. It has been specifically correlated with arthritis, pleuritis and especially amyloidosis. Patients with other mutations in the 694 and 680 codons can also have severe phenotypes. The V726A mutation, although identified in FMF patients with a relatively mild phenotype, has also been detected in patients with renal amyloidosis. E148Q is often associated with a mild phenotype, and whether it is even a polymorphism has been questioned. The MEFV gene codes for a protein that was respectively called pyrin and marenostrin by the French and international consortia that simultaneously identified the gene. Its function is still not determined, but it was recently colocalised with microtubules and actin filaments in the cytoplasm. It contains a death domain called PYD (Pyrin Domain), usually associated with proteins involved in apoptosis. Some genes have been tested to assess their possible modifying effects on clinical features of FMF. The alpha/alpha genotype of the serum amyloid A or SAA1 gene is associated with an increased risk of amyloidosis in FMF patients, especially in patients homozygous for M694V, whereas the MICA (Major Histocompatibility Complex, MHC class-I-chain-related type A) gene seems to have an effect on disease course but not its clinical manifestations. The most effective treatment for FMF patients is colchicine, which should be taken regularly on a life-long basis. It decreases the frequency and severity of crises and prevents renal amyloidosis.
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PMID:[Familial Mediterranean Fever (FMF): from diagnosis to treatment]. 1574 78


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